Developing a spectroscopic toolkit for probing protein structure and folding

描述（由申请人提供）：从分子角度理解蛋白质折叠是现代生物物理学的核心挑战之一。目前的实验技术只能提供相对有限的生物分子在溶液中经历的超快波动和远程构象变化的观点。该项目的第一个目标是开发一个基于超快多维红外光谱的实验框架，该框架将以亚皮秒的时间分辨率测量蛋白质结构，提供折叠，变性和蛋白质聚集等非平衡过程的详细视图。实验数据将得到尖端分子动力学模拟的支持，这是由于分布式计算的最新发展，以及提供分子结构和振动频率之间联系的结构-频率图。该项目的另一个组成部分将致力于开发一种通用的实验方法，从分析的角度来量化溶液中蛋白质的结构，目标是实现测量球形蛋白质的结构、构象灵活性和溶剂暴露的方法。

DESCRIPTION (provided by applicant): Understanding protein folding from a molecular perspective is one of the central challenges in modern biophysics. Current experimental techniques only provide a relatively limited view of the ultrafast fluctuations and long-range conformational changes that biomolecules undergo in solution. The first objective of this project is to develop an experimental framework based on ultrafast multidimensional infrared spectroscopy that will measure protein structure with sub- picosecond time resolution, offering a detailed view of non-equilibrium processes such as folding, denaturation, and protein aggregation. The experimental data will be supported by cutting-edge molecular dynamics simulations, which are now possible due to recent developments in distributed computing, as well as structure-frequency maps that provide the connection between molecular structures and vibrational frequencies. Another component of the project will aim at developing a general experimental method to quantify the structure of proteins in solution from an analytical perspective with the goal of implementing methods for measuring the structure, conformational flexibility, and solvent exposure of globular proteins.